Integrated Human Practices
Abstract
Human Practice and its integration to the project should be conducted with a suitable methodology formed in an introspective framework, and our Human Practice was designed based on the “Intervention Model" presented in the section below.
Each time we reached the turning points of strategy in the project development, we observed our whole team and continually kept the Human Practice cycle going with building new methodology construction.
Human Practices were divided into three sections based on our observations. Each had its own focus and strategy:
- Section 0: Starting the project and recognizing the characteristics of our team
- Section 1: Exploring social issues to tackle and proposing solutions
- Section 2: Constructing foundational solution - SWIFT
- Section 3: Implementing SWIFT in various potential fields
By establishing methodologies in each section of the project development process, we have reassessed the governance recognition of the members. This method enhanced our project’s compatibility with the world, and contributed to proposing a better society with SWIFT.
Governance of human practices - introducing “Intervention Model"
Human practices as “Clinical" activities
"Human Practices is the study of how your work affects the world, and how the world affects your work." (Peter Carr, Director of Judging)
The mission of human practice can be described as establishing interconnections between the project and the world. In this context, human practice should not solely focus on achieving certain output, like tasks in the Dry lab or Wet lab, but should actively engage in and exert influence on project governance.
So, how should we carry out human practice? Project governance is not solely shaped by the explicit knowledge embodied in frameworks like the Engineering Cycle, but also depends on the tacit knowledge embedded within teams and their laboratories. Therefore, even when we introduce excellent frameworks proposed by previous teams, such as 2019_Exeter, we cannot effectively manage the project unless we are aware of the tacit knowledge within our own teams.
Hence, we propose the concept of viewing human practice as “clinical activity."
Clinical activity originally pertains to activities involving the physical and mental health of others. We have specifically drawn inspiration from clinical psychology as an illustrative reference. Clinical psychologists aim to identify and control factors that impact their clients' well-being to guide them toward improved states. This process is referred to as “intervention". Client conditions vary significantly from person to person, and psychologists initiate the process by observing and describing these conditions before pinpointing and influencing the relevant factors.
Building upon this understanding, we define human practice as "the interaction between the project and society, conducted as a result of ‘intervention’ that teams undertake within the project execution process to make the project more responsible and beneficial for the world." We have endeavored to construct a framework around this concept of “intervention" in clinical psychology, drawing support from the concept of episodic description in developmental psychology. Our goal is to develop an approach that can be applied to the general project governance of iGEM. This is what we refer to as the “Intervention Model."
Intervention Model
The Intervention Model comprises three steps:
Step1. Observation: To observe the project's execution methods embodied within the team.
Step2. Methodology Construction: To establish an intervention methodology based on the observations.
Step3. Intervention: To engage the entire team in a dialogue about its own governance, resulting in changes to the project's execution.
The observation process means our team members proceed with the project simultaneously observing the team from a meta-perspective. This so-called 'participant observation' is highly effective in describing and understanding the team's embodied unique knowledge and routines. It's important to note that some bias is inherent in participant observation. Therefore, we adopt this episodic description, inspired by developmental psychology, to help readers relativize bias.
Episodic description focuses on specific episodes, where the writer first describes the episode's background and context, followed by a description of the episode itself. Finally, the writer provides an analysis, akin to interpreting a memory, reflecting on the episode's observations from a meta-perspective. This approach enables readers to retrace the writer's thoughts in episode selection, content, and interpretation. Comparing their current perspectives with those of the writer at the time, the readers inevitably conduct relativization.
In the process of methodology construction, we analyze how to intervene in a present project progress based on our observations. The team contemplates how to evolve our embodied governance methodologies to make the project responsible and good for the world. Subsequently, we formulate intervention plans. When devising these plans, we may either create our unique methodologies or leverage frameworks established by past iGEM teams.
The intervention process entails the actual implementation of the constructed methodologies and their impact on project governance. This may involve controlling factors that influence governance, such as external environmental variables (e.g., encouraging to proactively reach out to stakeholders in specific contexts), or consciously altering governance methodologies.
How to govern human practices
The Intervention Model stands out for its unique approach, positioning Human Practice as the cornerstone of project governance, rather than a red tape, which is merely a process for obtaining results. We firmly believe that the active engagement of team members with a higher-dimension perspective could be an institutional guarantee for Human Practice in governing project execution effectively.
In practical terms, this model proves most valuable during the initial stages of project development, where annual planning and execution are paramount. Furthermore, as the project progresses, it necessitates a continuous cycle of observation, methodology development, and intervention.
To enhance the project comprehensively, it is crucial to grasp all aspects, including the tacit knowledge embedded within the team, and to implement progressive interventions. The Intervention Model aims to fulfill this requirement, striving to bring transparency and visibility to project governance.
Practices for the current year
Section 0: Starting the Project and Recognizing the Characteristics of Our Team
Prior to conducting the actual Human Practice, we observed our team and developed a Human Practice methodology based on the observations.
Observation
The entire team showed a keen interest in the cellular therapy market and aimed to address current challenges in cellular therapy using synthetic biology or to develop new therapies through a cellular therapeutic approach. We wanted this year's project to be related to this fascinating field, but were undecided about the specific subject of the survey.
Methodology Construction
This was our Human Practice methodology established for the next section 1. First, we decided to conduct interviews with cell therapy experts to identify the challenges associated with current cell therapy practices. Then selective assessment of the issues to address should be guided by the team's curiosity. We were to formulate hypotheses on how these challenges could potentially be resolved using synthetic biology with interviews of experts. Carrying out this process iteratively, we were aiming to identify more specific problems amenable to solutions and concrete methods of addressing them.
Section 1: Exploring Social Issues to Tackle and Proposing Solutions
In this section of Human Practice, we seeked to identify social challenges and investigate potential synthetic biology approaches to address these challenges.
Our focus was on the cell therapy market, particularly the prominent CAR-T cell therapy, which is associated with a major side effect known as CRS (Cytokine Release Syndrome).
We planned to gain insights into existing CRS coping measures and its pathogenesis through the communications with clinicians and researchers. Then we aimed to identify areas where current therapies fall short and explore how synthetic biology approaches could address these gaps.
Prof. Yuki Kagoya
Keio University, Facluty of Medicine, Institute for Advanced Medical Research
About CAR-T therapy: current status and the problem aim to find out the problems of the therapy
Dr. Keishi Adachi
Department of Immunology, Faculty of Medicine, Yamaguchi University
Multiple Concerns About the Cost of CAR-T Cell Therapy
Prof. Yoshiyuki Takahashi
Nagoya University Faculty of Medicine, Department of Pediatrics
Financial Toxicity and CRS of the Promising Cancer Therapy
Prof.Yuki Kagoya
Keio University, Facluty of Medicine, Institute for Advanced Medical Research
Discovering the Importance of Swiftness
Dr. Hidefumi Hiramatsu
Kyoto University Hosipital, Department of Pediatrics
Opinions from a Clinician
Prof. Keiichiro Mihara
Fujita Helth University, International Center for Cell and Gene Therapy
Need to Suppress Other Cytokines as Well
Prof. Akihiko Yoshimura
Keio University, Facluty of Medicine, Microbiology/Immunology
Meet Extensibility and Where to Apply It Beyond CRS
The First Observation of The Previous Process
Our project has thus far identified the issues with current cell therapy and proposed solutions to the issues of dealing with CRS that we have decided to tackle. However, we realized that there was a problem that could not be controlled by conventional transcriptional regulation systems, so all members worked together to create a higher-order control system than transcriptional regulation. Originally, the members were interested in creating a more basic system, and when Professor Yoshimura pointed out the possibility of creating a foundational system, all of them came to have the idea that we wanted to pursue something more foundational. This is our turning point.
The First Reconstruction How to Conduct The Human Practice
In Section 2 of Human Practice, we conducted interviews mainly with academic researchers in order to assure the system as a foundational one. Our goal was not only to fill in the technical problems pointed out in Section 1, but also to make our system more expandable, involving the situations and results of the Dry lab and Wet lab. We have decided to use this Human Practice cycle to resolve concerns and suggestions.
Section 2: Constructing Foundational Solution - SWIFT
Through Human Practice in the preceding section, we learned that 'speed' and 'scalability' are critical factors when addressing CRS. Additionally, we received feedback suggesting that a system with these attributes could have broader applications beyond CRS and possess versatility. Thus, we named this adaptable system 'SWIFT.'
We started to identify technical challenges that SWIFT needed to address to be a foundational system and explore corresponding solutions through Human Practice involving researchers primarily from academia.
Dr. Koushi Hidaka
Kobe University Research Facility Center for Science and Technology, Medicinal Chemistry and Chemical Biology
Proposal for Protease Amplifying
Associate Prof. Toru Terada
The University of Tokyo Faculty of Agriculture, Department of Biotechnology
First Step in Simulation Using Three Dimensional Structure
Prof. Munehito Arai
The University of Tokyo, School of Arts and Science, Department of Life Science
The Second Step in Simulation Using Three Dimensional Structure
Prof. Yoko Shiba
Iwate University, Graduate School of Arts and Sciences, Division of Science and Engineering, Graduate course of Biological Sciences, Laboratory of intracellular traffic
Dealing with ER Stress and Advantages Over Existing Systems
Dr. Joshua Leonard
Associate Professor of Chemical and Biological Engineering, Northwestern University
Potential Application of MESA to Other Cells
The Second Observation of the Previous Process
Up until this point, the team had been very focused on basic technology, and had been in contact with only academic researchers to ask about technical improvements. By having the Dry lab and Wet lab come together to share their concerns and suggestions, it can be seen that the Human Practice team was able to implement appropriate interventions in line with their concerns.
However, there was a problem in that the team was so focused on the basic technology that they were unable to see a society that would actually implement SWIFT.
The Second Reconstruction How to Conduct the Human Practice
At that time we had completed SWIFT as a fundamental technology, we felt the need to focus more on society than ever before and work to optimize SWIFT for each implementation.
We firstly brainstormed in which situations SWIFT, as a fundamental technology, could be used. The results are shown below.
Section 3: Implementing SWIFT in Various Potential Fields
In this section, we conducted Human Practice with a focus on optimizing SWIFT, a technically completed foundational technology, for CRS applications. Additionally, considering ‘the whole society’, including medical professionals and companies, we conducted Human Practice to explore potential uses of SWIFT beyond CRS and to optimize it for various specific demands such as medicine, material production, environment, and agriculture.
We moved on to optimizing SWIFT to every possible vision of implementation, not only CRS but beyond it; medicine, material production, environment, and agriculture. This process was to involve “the whole society", professionals and companies in various fields.
Click icon to see each roadmap
Prof. Takanori Teshima
Hokkaido University, Facluty of Medicine, Division of Internal Medicine
Proposal to Introduce Genes to MSC
Prof. Kazuma Tomizuka
Tokyo University of Pharmacy and Life Sciences, Department of Applied Life Sciences
MSC's Strengths and Weaknesses
Anonymous
Visions of Implementation
Prof. Shintaro Hojo & Dr. Hiroki Tanaka
Hokkaido University, Facluty of Medicine, Division of Molecular Psychoneuroimmunology
SWIFT's Strengths in Addressing CRS
Prof. Koichi Setoyama
Kyoto Prefectural University of Medicine, Professor of Biomedical Ethics, PhD. in Law
ELSI Consideration for CRS Implementation
The Third Observation of the Previous Process
In Section 3, the team was desperate to find situations where SWIFT could be applied, and after having conducted Human Practice only with researchers in academia up to Section 2, the main focus in Section 3 was to conduct Human Practice with companies and organizations.
The Third Reconstruction How to Conduct the Human Practice
In Section 3, the main focus was conducting Human Practice with companies and organizations for each implementation destination, which made it difficult to optimize specific technologies.
Therefore, from now on, the priority will be to deepen the vision of specific technical implementation by conducting Human Practice that includes researchers.
Seeing the Future Through SWIFT
Consideration for Implementation
SWIFT is being implemented in a wide range of fields, including not only the medical sector, such as CRS, which was initially considered for implementation, but also material production, environmental applications, and implementations related to plant and agriculture. Detailed information regarding these implementation methods can be found in Proposed Implementation Page. Here, you can learn about the necessary design and procedures for introducing SWIFT into the real world.
Team Growth through Human Practice
When we received harsh feedback from experts and stakeholders through Human Practice, it was not uncommon for us to feel anxious and even despair, fearing that the project might collapse.
However, with each iteration of our Human Practice, our team also developed the resilience to rise up and transform SWIFT into something better.
In pursuit of a future where our activities would have a significant impact on society, we eagerly absorbed any suggestions, at times even the harshest opinions, from experts and stakeholders as valuable hints to create substantial value.
Through Human Practice, not only SWIFT but also our team members were able to undergo substantial growth.
SWIFT Never Stops its Stride
We understand that SWIFT's journey through Human Practice is far from over, and we are currently at a stage where we have received only hints for its implementation in the fields of medicine, material production, plant, agriculture, and the environment. For each of these implementation areas, we need to engage more closely with stakeholders, optimize SWIFT's design, consider ethical, legal, social implications (ELSI) and safety aspects, and continue investigating the processes required for their real-world implementation.
We have made an initial step toward its implementation in various real-world contexts, accomplished the development of SWIFT as a foundational technology and have identified scenarios where SWIFT could bring societal benefits.
Now, the journey of further Human Practice begins, aimed at optimizing SWIFT for each of these specific implementations.
References
-
Norelli, M., Camisa, B., Barbiera, G., Falcone, L., Purevdorj, A., Genua, M., ... & Bondanza, A. (2018). Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nature medicine, 24(6), 739-748. https://doi.org/10.1038/s41591-018-0036-4 ↩ ↩2
-
Rose-John S. (2012). IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. International journal of biological sciences, 8(9), 1237–1247. https://doi.org/10.7150/ijbs.4989 ↩ ↩2
-
Oliai, C., Crosetti, A., De Vos, S., Eradat, H., Mead, M. D., Larson, S. M., ... & Timmerman, J. (2021). IL-1 receptor antagonist for prevention of severe immune effector cell-associated neurotoxicity syndrome. https://doi.org/10.1200/JCO.2021.39.15_suppl.7566 ↩ ↩2
-
Sterner, R. M., Sakemura, R., Cox, M. J., Yang, N., Khadka, R. H., Forsman, C. L., Hansen, M. J., Jin, F., Ayasoufi, K., Hefazi, M., Schick, K. J., Walters, D. K., Ahmed, O., Chappell, D., Sahmoud, T., Durrant, C., Nevala, W. K., Patnaik, M. M., Pease, L. R., . . . Kenderian, S. S. (2019). GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood, 133(7), 697-709. https://doi.org/10.1182/blood-2018-10-881722 ↩
-
Prasenjit Bhaumik, Huogen Xiao, Koushi Hidaka, Alla Gustchina, Yoshiaki Kiso, Rickey Y. Yada, and Alexander Wlodawer. (2011). Structural Insights into the Activation and Inhibition of Histo-Aspartic Protease from Plasmodium falciparum. Biochemistry, 50 (41), 8862-8879. https://doi.org/10.1021/bi201118z ↩
-
Wu, J., Kaufman, R. From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ 13, 374–384 (2006). https://doi.org/10.1038/sj.cdd.4401840 ↩